Nanoscale Horizons
·
2024
·
IF 8
Yue Chen,Tong Ding,Zhengzheng Qian,Zerui Ma,Liming Zhou,Zhiling Li,Runkai Lv,Yinghui Xu,Yingjie Xu,Linhui Hao,Chen Zhu,Xikuang Yao,Wenying Yu,Wenpei Fan
Sonodynamic therapy (SDT) is gaining popularity in cancer treatment due to its superior controllability and high tissue permeability. Nonetheless, the efficacy of SDT is severely diminished by the transient generation of limited reactive oxygen species (ROS). Herein, we introduce an acid-activated nanosonosensitizer, CaO2@PCN, by the controllable coating of porphyrinic metal-organic frameworks (PCN-224) on CaO2 to induce cascaded oxidative stress in tumors. The PCN-224 doping could generate ROS during SDT to induce intracellular oxidative stress and abnormal calcium channels. Meanwhile, the ultrasound also promotes extracellular calcium influx. In addition, the CaO2@PCN will sequentially degrade in the tumor cell lysosomes, releasing Ca2+ and H2O2 to induce further abnormal calcium channels and elevate the levels of Ca2+. Insufficient catalase (CAT) in tumor cells promotes intracellular calcium overload, which can induce persistent ROS generation and mitochondrial dysfunction through ion interference therapy (IIT). More importantly, PCN-224 also protects CaO2 against significant degradation under neutral conditions. Hence, the well-designed CaO2@PCN produces synergistic SDT/IIT effects and persistent ROS against cancer. More notably, the acidity-responsive biodegradability endows CaO2@PCN with excellent biosafety and promising clinical potential.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 12
·2202424
·
IF 10
Dongdong Guo,Xiaoyong Dai,Kewei Liu,Yuhong Liu,Jiamin Wu,Kun Wang,Shengwei Jiang,Fen Sun,Lijun Wang,Bing Guo,Dongye Yang,Laiqiang Huang
While calcium-overload-mediated therapy (COMT) is a promising but largely untapped therapeutic strategy, combinatory therapy greatly boosts treatment outcomes with integrated merits of different therapies. Herein, a BPQD@CaO 2 -PEG-GPC3Ab nanoplatform is formulated by integrating calcium peroxide (CaO 2 ) and black phosphorus quantum dot (BPQD, photosensitizer) with active-targeting glypican-3 antibody (GPC3Ab), for combinatory photodynamic therapy (PDT) and COMT in response to acidic pH and near-infrared (NIR) light, wherein CaO 2 serves as the reservoir of calcium ions (Ca 2+ ) and hydrogen peroxide (H 2 O 2 ). Navigated by GPC3Ab to tumor cells at acidic pH, the nanoparticle disassembles to CaO 2 and BPQD; CaO 2 produces COMT Ca 2+ and H 2 O 2 , while H 2 O 2 makes oxygen (O 2 ) to promote PDT; under NIR irradiation BPQD facilitates not only the conversion of O 2 to singlet oxygen ( 1 O 2 ) for PDT, but also moderate hyperthermia to accelerate NP dissociation to CaO 2 and BPQD, and conversions of CaO 2 to Ca 2+ and H 2 O 2 , and H 2 O 2 to O 2 , to enhance both COMT and PDT. After supplementary ionomycin treatment to induce intracellular Ca 2+ bursts, the multimodal therapeutics strikingly induce hepatocellular carcinoma apoptosis, likely through the activation of the calpains and caspases 12, 9, and 3, up-regulation of Bax and down-regulation of Bcl-2 proteins. This nanoplatform enables a mutually-amplifying and self-reinforcing synergistic therapy.
研究领域:
癌症治疗
·
纳米技术
·
光动力疗法
·
钙信号
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yuzhao Zheng,Fanxue Bu,Chenfeng Xu,Tongyu Wu,Jianping Zhou,Weiyang Shen,Tingjie Yin
Immunosuppressive microenvironment and poor immunogenicity are two stumbling blocks in anti-tumor immune activation. Tumor associated macrophages (TAMs) play crucial roles in immunosuppressive microenvironment, while immunogenic cell death (ICD) is a typical strategy to boost immunogenicity. Herein, we developed a coordinative modular assembly-based self-reinforced nanoparticle, (CaO 2 /TA)-(Fe 3+ /BSA) which integrated CaO 2 , Fe 3+ -tannic acid coordinated networks and albumin under the instruction of molecular dynamics simulation. (CaO 2 /TA)-(Fe 3+ /BSA) could significantly enhance Fenton reaction through Fe 3+ self-reduction and H 2 O 2 self-sufficiency, and simultaneously increased intracellular accumulation of Ca 2+ . The self-augmented Fenton reaction with sufficient reactive oxygen species effectively repolarized TAMs and elicited ICD with Ca 2+ overload. Besides, (CaO 2 /TA)-(Fe 3+ /BSA) was confirmed to self-reinforce deep tumor drug delivery by “treatment-delivery” positive feedback based on gp60-mediated transcytosis and M2-like macrophages repolarization-mediated perfusion promotion. Resultantly, (CaO 2 /TA)-(Fe 3+ /BSA) effectively alleviated immunosuppression, provoked local and systemic immune response and potentiated anti-PD-1 antibody therapy. Our strategy highlights a facile and controllable approach to construct penetrated effective antitumor nano-immunotherapeutic agent.
研究领域:
癌症免疫治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Yunsu Ma,Huanghuang Xu,Bo Sun,Silin Du,Shuai Cui,Li Zhang,Ning Ding,Dongzhi Yang
The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O2 and H2O2 self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co2+ and release CaO2 and graphene quantum dots (GQDs). The exposed CaO2 reacted with water to generate H2O2 and O2. The self-supplied O2 alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H2O2 was catalyzed by endogenous Co2+ to produce hydroxyl radicals for Co2+-triggered CDT. In vitro and in vivo experiments confirm that CaO2/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO2/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO2/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP–AMP synthase–stimulator of interferon genes signaling pathway.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
传染病
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Yihan Wang,Changnan Xie,Zhiming Zhang,Haining Liu,Haixia Xu,Ziyue Peng,Chun Liu,Jianjun Li,Chengqiang Wang,Tao Xu,Lixin Zhu
The repair of large bone defects remains a challenging problem in bone tissue engineering. Ischemia and hypoxia in the bone defect area make it difficult for seed cells to survive and differentiate, which fail to perform effective tissue regeneration. Current oxygen-producing materials frequently encounter problems such as a rapid degradation rate, insufficient mechanical properties, difficult molding, and cumbersome fabrication. Here, a novel three-dimensional (3D) printed integrated bionic oxygenated scaffold was fabricated with gelatin-CaO2 microspheres, polycaprolactone (PCL), and nanohydroxyapatite (nHA) using low-temperature molding 3D printing technology. The scaffold had outstanding mechanical properties with bionic hierarchical porous structures. In vitro reports showed that the scaffold exhibited excellent cytocompatibility and could release O2 sustainably for more than 2 weeks, which significantly enhanced the survival, growth, and osteogenic differentiation of bone marrow mesenchymal stem cells under hypoxia. In vivo experiments revealed that the scaffold facilitated efficient bone repair after it was transplanted into a rabbit calvarial defect model. This result may be due to the scaffolds reducing hypoxia-inducible factor-1α accumulation, improving the expression of osteogenic regulatory transcription factors, and accelerating osteogenesis. In summary, the integrated bionic PCL/nHA/CaO2 scaffold had excellent capabilities in sustainable O2 release and bone regeneration, which provided a promising clinical strategy for bone defect repair.
研究领域:
组织工程
·
生物医学工程
·
再生医学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xiaoli Feng,Tian Lin,Dong Chen,Zhiyang Li,Qiuping Yang,Huiting Tian,Yao Xiao,Mingzhen Lin,Min Liang,Weihong Guo,Peng Zhao,Zhaoze Guo
Chemodynamic therapy (CDT) can effectively induce immunogenic cell death (ICD) in tumours and is thus a promising strategy for boosting the efficacy of immunotherapy. However, the mechanism by which CDT enhances ICD and lowers ICD efficiency is unknown and this restricts its clinical application. In this study, a second near-infrared (NIR-II) window irradiation-triggered hydrogen peroxide (H 2 O 2 ) self-supplying nanocomposite ((Cu 2 Se-CaO 2 )@LA) was constructed. The modified lauric acid was melted by the heat energy of the NIR-II irradiation, to expose the CaO 2 nanoparticles, and they then reacted with water to produce H 2 O 2 and Ca 2+ . H 2 O 2 was then converted to hydroxyl radicals by the photothermal-enhanced CDT process of the Cu 2 Se nanocubes. Notably, the CDT and Ca 2+ overload was found to induce sequential damage to the mitochondria and endoplasmic reticulum (ER), which upregulated the PERK-mediated eIF2α phosphorylation pathway and caused subsequent ICD. NIR-II irradiation of the (Cu 2 Se-CaO 2 )@LA also increased reactive oxygen species (ROS) formation and this was sufficient to increase dendritic cell maturation, attracting cytotoxic T lymphocytes, and suppressing tumour growth in vivo. Overall, we demonstrated that an enhanced CDT strategy under NIR-II exposure and H 2 O 2 self-supply can induce extensive ICD by inducing mitochondria-associated ER stress, which represents a highly effective and promising strategy for ICD amplification and tumour immunotherapy. Statement of significance In this study, a second near-infrared window (NIR-II) irradiation-triggered and H 2 O 2 self-supplying nanocomposite (named (Cu 2 Se-CaO 2 )@LA) was constructed and tested both in vitro and in vivo . These nanoparticles demonstrated promising antitumor activity as designed. Mechanistically, the nanoparticles could damage mitochondria and upregulate the PERK-mediated eIF2αphosphorylation pathway, further causing endoplasmic reticulum stress, and inducing immunogenic cell death through dendritic cell maturation and cytotoxic T lymphocyte recruitment augmented activity. This system represents a highly effective and promising strategy for enhancing tumor immunotherapy and provides new insights for future studies and design refinements.
研究领域:
癌症研究
·
免疫治疗
·
纳米技术
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Junjie Wu,Peng Shen,Xian Qin,Yulu Yang,Chuanchuan Lin,Xuan Li,Wenbo Geng,Pengfei Gao,Lixue Chen,Li Miao,Yang Jiao,Bailong Tao
Bacterial wound infection is a major challenge to human health worldwide. In this study, a composite nanogenerator, CaO 2 @ZIF-67-PLL, was fabricated via a bottom-up approach with chemodynamic therapy (CDT)/hypoxia improvement for rapid therapy of biofilm-infected wounds. Under a pathologically acidic microenvironment, the out layer ZIF-67 can be decomposed to rapidly release Co 2+ and CaO 2 ; Subsequently, the unprotected CaO 2 reacts with H 2 O to produce O 2 and H 2 O 2 . The self-supply of O 2 relieves hypoxia and inflammatory response induced by infections, while the generated H 2 O 2 and poly- l -lysine (PLL) exhibited synergistic strong anti-biofilm capability against Escherichia coli ( E. coli) and Staphylococcus aureus (S. aureus) as assessed by reactive oxygen species (ROS) generation, membrane permeability change, ATP reduction, o -nitrophenyl-β-d-galactopyranoside (ONPG) hydrolysis and intracellular component leakage. Meanwhile, CaO 2 @ZIF-67-PLL exhibited good cytocompatibility and promoted the adhesion, proliferation, and migration of NIH-3T3 cells by enhancing the expression of wound healing-related genes (TGF-β1, VEGF, α-SMA, Col I, Col III, and Wnt-5a). Notably, CaO 2 @ZIF-67-PLL could significantly improve the healing process of S. aureus -infected wounds via suppressed inflammatory responses, enhanced collagen disposition and angiogenesis, and stimulated HIF-1α, CD31, and Wnt-5a/β-Catenin signaling pathways. These results indicated the potential of CaO 2 @ZIF-67-PLL nanogenerator for clinical application in infected wound treatment.
研究领域:
纳米技术
·
生物医学工程
·
伤口愈合
·
感染控制
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）